Treatment of HIV Infection

When AIDS (acquired immunodeficiency syndrome) was first recognized in 1981, patients with the disease were unlikely to live longer than a year or two. Since then, scientists have developed an effective arsenal of drugs that can help many people infected with HIV (human immunodeficiency virus) live longer and healthier lives.

The treatment and prevention of HIV is a high priority for the National Institute of Allergy and Infectious Diseases (NIAID). Research supported by NIAID has greatly advanced our understanding of HIV and how it causes AIDS. This knowledge provides the foundation for NIAID AIDS research effort and continues to support studies designed to further extend and improve the quality of life of those infected with HIV.

Drugs for HIV Infection

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Twenty drugs have been approved by the Food and Drug Administration to treat individuals infected with HIV. They are called antiretroviral drugs because they attack HIV, which is a retrovirus. After entering the host cell, HIV uses specific enzymes to survive and multiply. The first approved classes of antiretroviral drugs work by interfering with the virus' ability to use these enzymes. These drugs fall into two categories.

Reverse transcriptase (RT) inhibitors -- RT inhibitors interfere with an enzyme called reverse transcriptase that HIV needs to make copies of itself. There are two main types of RT inhibitors, and they each work differently.

Nucleoside/nucleotide drugs provide faulty DNA building blocks, halting the DNA chain that the virus uses to make copies of itself

The newest class of antiretroviral drugs works by changing the shape of the outer covering of the HIV virus. This class of drugs is called fusion inhibitors. Fusion inhibitors interfere with the virus' ability to fuse with the cellular membrane, thereby blocking entry into the host cell.

Drugs Approved for HIV Infection

Nucleoside/Nucleotide RT Inhibitors

Non-nucleoside RT Inhibitors

Protease Inhibitors

Fusion Inhibitors

abacavir

delavirdine

ritonavir

enfuvirtide

ddC

nevirapine

saquinavir

ddI

efavirenz

indinavir

d4T

amprenavir

3TC

nelfinavir

ZDV

lopinavir

tenofovir

atazanavir

entricitabine

fosamprenavircalcium

Do Antiretroviral Drugs Cure HIV Infection?

Currently available drugs do not cure HIV infection. They can suppress HIV but are unable to completely eliminate it from the body. Because HIV can become resistant to any one drug, people with HIV infection must take a combination of antiretroviral drugs to suppress the virus. The combination of drugs, usually from at least two classes, is referred to as highly active antiretroviral therapy (HAART). NIAID-supported researchers and drug companies developed HAART regimens that are safe and effective.

Although the use of HAART has greatly reduced the number of deaths due to HIV, this powerful combination of drugs cannot suppress the virus completely. People infected with HIV who receive antiretroviral drugs can still transmit HIV to others through unprotected sex and needle sharing.

People with HIV infection have impaired immune systems which can no longer protect them against infections. These opportunistic infections (OIs) and AIDS-associated co-infections are caused by a wide range of microorganisms such as protozoa, viruses, fungi, and bacteria. One example is hepatitis C virus (HCV) infection which can lead to liver cancer. Examples of harmful physiological effects caused by other OIs or co-infections include altered body fat distribution, insulin resistance, elevated triglycerides and cholesterol levels, and bone loss.

Potent HIV therapies such as HAART, however, have produced dramatic responses in patients by suppressing HIV, thereby slowing the progression of OIs and AIDS-associated co-infections. These therapies also sustain the immune system that can protect the body from other infections. Hence, antiretroviral drugs provide a way for the immune system to remain intact and effective, and thereby improving the quality of life for people with HIV.

Occasional Barriers Associated With Antiretroviral Drug Use

People with HIV take medicines with complicated regimens, often taking several drugs per day and some of which may require fasting. Hence, some people may have difficulty adhering to these complicated regimens, find the food restrictions difficult to deal with, and may experience unpleasant side effects such as nausea and vomiting. Therefore, NIAID is studying simpler regimens with newer antiretroviral drugs.

Aside from the complicated dosing regimens, antiretroviral drugs themselves may cause medical problems. Metabolic changes can occur in people with HIV taking antiretroviral drugs. They may include abnormal fat distribution, abnormal lipid and glucose metabolism, and bone loss.

NIAID Research on the Complications of Anti-HIV Drugs

NIAID supports studies aimed at understanding the side effects of drugs or combinations of drugs as well as strategies to reduce exposure to potentially toxic drug regimens, such as

Structured treatment interruption (STI) protocols

Use of immune-based therapies with HAART

Studies to compare different dosing schedules

Studies to compare early versus delayed treatment

NIAID also supports projects evaluating regimens containing agents associated with toxicities. For example, NIAID-funded researchers are investigating treatments for some metabolic complications. There are ongoing studies evaluating various treatments of fat redistribution, lipid and glucose abnormalities, and bone loss.

In addition, researchers are studying the metabolic effects of various antiretroviral regimens in pregnant women and their infants and in HIV-infected children and adolescents. These studies include long-term follow-up.

Research to Ensure Safety of Drugs

NIAID supports the development and testing of new classes of antiretroviral compounds or combinations that will be able to continuously suppress the virus with few side effects. Such studies will provide accurate and extensive information about the safety of the new agents and combinations. They will identify potential uncommon, but important, toxicities of newly approved agents. Studies are also underway to assess rare toxicities of older approved agents, especially as a result of long-term use.

Through its Multicenter AIDS Cohort Study and Women's Interagency HIV Study, NIAID supports long-term studies of HIV disease in both men and women. Since their inception, these cohort studies have enrolled and collected data on more than 9,500 people. In addition to the information gleaned from this epidemiologic goldmine, other studies on the specific metabolic complications of HIV treatment are supported through both the adult and pediatric AIDS Clinical Trials Groups as well as through the Terry Beirn Community Programs for Clinical Research on AIDS.

New Drugs in the Pipeline

The Pharmaceutical Research and Manufacturers Association of America lists nearly five dozen new anti-HIV drugs currently in development as of 2003. (New Medicines in Development for HIV/AIDS 2003). They include new protease inhibitors and more potent, less toxic RT inhibitors, as well as other drugs that interfere with entirely different steps in the virus' lifecycle. These new categories of drugs include

Gene therapy -- modified genes inserted directly into cells to suppress HIV replication. These cells are designed to produce T cells that are genetically resistant to HIV infection.

In addition, scientists are learning how immune modulators help boost the immune system's response to the virus and may make the existing anti-HIV drugs more effective. Therapeutic vaccines are also being evaluated for this purpose and could help reduce the number of anti-HIV drugs needed or the duration of treatment.

More Information

AIDSinfo is a comprehensive resource for up-to-date information on government and industry sponsored HIV/AIDS treatment and prevention clinical trials. AIDSinfo also maintains the most current, federally approved guidelines for treating and preventing HIV/AIDS in adults and children, for AIDS-related illnesses, managing occupational exposure to HIV, and for preventing HIV transmission from mother-to-child during pregnancy. AIDSinfo is sponsored by the NIH Office of AIDS Research, NIAID, National Library of Medicine, Centers for Disease Control and Prevention, Health Resources and Service Administration, and Centers for Medicare and Medicaid Services.

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